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Updated: Dec 10, 2025
Ambulatory ECG Recording in Mice
Published on: May 27, 2010
Caspofungin Effects on Electrocardiogram of Mice: An Evaluation of Cardiac Safety
Danielle Cristiane Correa De Paula1, Elaine Amaral Leite2, Carolina Morais Araujo1
1Pharmaceutical Science Program (CiPharma), School of Pharmacy, Federal University of Ouro Preto, Campus Morro do Cruzeiro, s/n, Ouro Preto, Minas Gerais, 35400-000, Brazil.
Abstract:
Caspofungin is an echinocandin, exhibiting efficacy against most Candida species invasive infection. Its cardiotoxicity was reported in isolated rat heart and ventricular myocytes, but in vivo and clinical studies are insufficient. Our objective was to evaluate caspofungin in vivo cardiac effects using an efficacious dose against Candida albicans. Female Swiss mice were infected with C. albicans, and treated with caspofungin, 5 or 10 mg/kg, intraperitoneal along 5 days. Survival rate and colony-forming units (CFU) into vital organs were determined. For cardiac effects study, mice were treated with caspofungin 10 mg/kg, and electrocardiogram (ECG) signal was obtained on C. albicans-infected mice, single dose-treated, and uninfected mice treated along 5 days, both groups to measure ECG intervals. Besides, ECG was also obtained by telemetry on uninfected mice to evaluate heart rate variability (HRV) parameters. The MIC for caspofungin on the wild-type C. albicans SC5314 strain was 0.3 μg/ml, indicating the susceptible. Survival rate increased significantly in infected mice treated with caspofungin compared to mice treated with vehicle. None of the survived infected mice presented positive CFU after treatment with 10 mg/kg. C. albicans infection induced prolongation of QRS, QT, and QTc intervals; caspofungin did not alter this effect. Caspofungin induced increase of PR and an additional increase of QRS after 24 h of a single dose in infected mice. No significant alterations occurred in ECG intervals and HRV parameters of uninfected mice, after caspofungin treatment. Caspofungin showed in vivo cardiac relative safety maintaining its antifungal efficacy against C. albicans.
Insights
Caspofungin effectively treats Candida albicans infections in mice, showing improved survival and reduced fungal load. While infection prolonged ECG intervals, caspofungin demonstrated in vivo cardiac safety with minimal effects on heart rate variability.
Area of Science:
- Pharmacology
- Infectious Diseases
- Cardiology
Background:
- Caspofungin, an echinocandin, is effective against invasive Candida infections.
- Previous studies suggested potential cardiotoxicity in vitro, but in vivo data were limited.
- Echinocandin antifungal efficacy and safety require further in vivo investigation.
Purpose of the Study:
- To evaluate the in vivo cardiac effects of caspofungin during Candida albicans infection.
- To assess the efficacy of caspofungin in a murine model of invasive candidiasis.
- To determine the impact of caspofungin on electrocardiogram (ECG) parameters and heart rate variability (HRV).
Main Methods:
- Murine model of Candida albicans infection treated with caspofungin (5 or 10 mg/kg).
- Assessment of survival rates and fungal burden (colony-forming units) in vital organs.
- In vivo ECG recordings and HRV analysis in infected and uninfected mice.
Main Results:
- Caspofungin treatment significantly increased survival rates and eradicated Candida albicans in infected mice.
- Candida albicans infection prolonged QRS, QT, and QTc intervals; caspofungin did not exacerbate these changes.
- Caspofungin induced minor, transient PR and QRS interval increases in infected mice but showed no significant impact on ECG or HRV in uninfected mice.
Conclusions:
- Caspofungin demonstrates in vivo cardiac relative safety at efficacious doses against Candida albicans.
- The antifungal efficacy of caspofungin is maintained while exhibiting a favorable cardiac safety profile in vivo.
- Further clinical evaluation is warranted to confirm the cardiac safety of caspofungin in patients.
